PMID- 24474771 OWN - NLM STAT- MEDLINE DCOM- 20140506 LR - 20211021 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 111 IP - 4 DP - 2014 Jan 28 TI - Estrogen receptor alpha polymorphism in a species with alternative behavioral phenotypes. PG - 1443-8 LID - 10.1073/pnas.1317165111 [doi] AB - The evolution of behavior relies on changes at the level of the genome; yet the ability to attribute a behavioral change to a specific, naturally occurring genetic change is rare in vertebrates. In the white-throated sparrow (Zonotrichia albicollis), a chromosomal polymorphism (ZAL2/2(m)) is known to segregate with a behavioral phenotype. Individuals with the ZAL2(m) haplotype engage in more territorial aggression and less parental behavior than individuals without it. These behaviors are thought to be mediated by sensitivity to sex steroids, and the chromosomal rearrangement underlying the polymorphism has captured a prime candidate gene: estrogen receptor 1 (ESR1), which encodes estrogen receptor alpha (ERalpha). We therefore hypothesized that the behavioral effects of the ZAL2(m) rearrangement are mediated by polymorphism in ESR1. We report here that (i) the ESR1 promoter region contains fixed polymorphisms distinguishing the ZAL2(m) and ZAL2 alleles; (ii); those polymorphisms regulate transcription efficiency in vitro and therefore potentially do the same in vivo (iii); the local expression of ERalpha in the brain depends strongly on genotype in a free-living population; and (iv) ERalpha expression in the medial amygdala and medial preoptic area may fully mediate the effects of genotype on territorial aggression and parenting, respectively. Thus, our study provides a rare glimpse of how a chromosomal polymorphism has affected the brain and social behavior in a vertebrate. Our results suggest that in this species, differentiation of ESR1 has played a causal role in the evolution of phenotypes with alternative life-history strategies. FAU - Horton, Brent M AU - Horton BM AD - Department of Psychology, Emory University, Atlanta, GA 30322. FAU - Hudson, William H AU - Hudson WH FAU - Ortlund, Eric A AU - Ortlund EA FAU - Shirk, Sandra AU - Shirk S FAU - Thomas, James W AU - Thomas JW FAU - Young, Emily R AU - Young ER FAU - Zinzow-Kramer, Wendy M AU - Zinzow-Kramer WM FAU - Maney, Donna L AU - Maney DL LA - eng GR - R21MH090418/MH/NIMH NIH HHS/United States GR - T32 GM008602/GM/NIGMS NIH HHS/United States GR - 5T32GM008602/GM/NIGMS NIH HHS/United States GR - 1R01MH082833/MH/NIMH NIH HHS/United States GR - R01 DK095750/DK/NIDDK NIH HHS/United States GR - ImNIH/Intramural NIH HHS/United States GR - 1R01DK095750/DK/NIDDK NIH HHS/United States GR - R01 MH082833/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20140113 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Estrogen Receptor alpha) RN - 0 (Protein Isoforms) SB - IM MH - Animal Communication MH - Animals MH - Behavior, Animal/*physiology MH - Biological Evolution MH - Estrogen Receptor alpha/*genetics MH - Female MH - Gene Expression Regulation MH - Haplotypes MH - Male MH - Phenotype MH - *Polymorphism, Genetic MH - Promoter Regions, Genetic MH - Protein Isoforms/*genetics MH - Songbirds/*physiology PMC - PMC3910653 OTO - NOTNLM OT - estradiol OT - morph OT - reproductive tactics OT - testosterone COIS- The authors declare no conflict of interest. EDAT- 2014/01/30 06:00 MHDA- 2014/05/07 06:00 PMCR- 2014/07/28 CRDT- 2014/01/30 06:00 PHST- 2014/01/30 06:00 [entrez] PHST- 2014/01/30 06:00 [pubmed] PHST- 2014/05/07 06:00 [medline] PHST- 2014/07/28 00:00 [pmc-release] AID - 1317165111 [pii] AID - 201317165 [pii] AID - 10.1073/pnas.1317165111 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2014 Jan 28;111(4):1443-8. doi: 10.1073/pnas.1317165111. Epub 2014 Jan 13.